Réaction #605409

Équation de réaction

NaOH

(E)-3-{3,4-Dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester hydrochloride

phenyl-acetaldehyde

NaCNBH3

→

(E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester

Rendement 89.4%

Solvants

MeOH

AcOH

MeOH

Conditions de réaction

Traitement

1. 1
   Autrethe solvent was removed
2. 2
   Autrethe residue partitioned between 5% aqueous NaHCO3 and DCM
3. 3
   SéchageThe organic phase was dried over Na2SO4
4. 4
   Autreevaporated
5. 5
   AutreThe crude product was purified by column chromatography (eluent: DCM/MeOH 95:5)

Mode opératoire

(E)-3-{3,4-Dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester hydrochloride (obtained as described in Example 25, Step B, 300 mg, 0.886 mmol) was dissolved in MeOH (30 ml). The pH was adjusted to 5 with AcOH and 1 M NaOH in MeOH, and then phenyl-acetaldehyde (128 mg, 1.06 mmol) and NaCNBH3 (67 mg, 1.06 mmol) were added. The mixture was stirred overnight at RT, then the solvent was removed and the residue partitioned between 5% aqueous NaHCO3 and DCM. The organic phase was dried over Na2SO4 and evaporated. The crude product was purified by column chromatography (eluent: DCM/MeOH 95:5) to give (E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (322 mg).

Source